Cyclopropylamine (CAS) [765-30-0] is an important intermediate in the synthesis of many important organic compounds. For example, cyclopropylamine is a useful intermediate for the synthesis of 6-cyclopropylamino-2-chloro-s-triazine herbicides. It is also an intermediate for the synthesis of cyromazine; N-cyclopropyl-1,3,5-triazine-2,4,6-triamine; an ectoparasiticide marketed by Ciba-Geigy and formulated as Vetrazine.RTM., Larvadex.RTM. and Trigard.RTM..
Previously, the route to cyclopropylamine was via cyclopropane carbonitrile. This is hydrolyzed to cyclopropane carboxamide in aqueous acid. This is then converted to cyclopropylamine by the Hofmann reaction in alkali hypochlorite and alkali hydroxide solution.
Recently, U.S. Pat. No. 3,711,549 disclosed converting gamma-butyrolactone to cyclopropylamine by cleaving gamma-butyrolactone in the presence of zinc chloride at 120.degree. C. at 300 psig. The resultant 4-chlorobutyric acid is then esterified with methanol to form 4-chlorobutyrate methyl ester. This ester is then cyclized to form the cyclopropanecarboxylic acid methyl ester. This cyclization reaction requires pre-esterification of the acid as the cyclization conditions would otherwise merely result in conjugation polymerization of the butyric acid moiety or ring closure to reform .gamma.-butyro-lactone. According to this patent, the resulting cyclopropane carboxylate ester, after closing the cyclopropane ring, is then amidated with gaseous ammonia under anhydrous conditions in the presence of toluene and sodium methoxide to form cyclopropanecarboxamide. While 90% conversion of the ester is reported, this figure includes repeated recycling of the unreacted cyclopropane carboxylate methyl or ethyl ester in the toluene solution.
This reaction requires toluene as the medium for the sodium methoxide reaction, as low overall yields of amide are reported when toluene is not used. The cyclopropane carboxamide is then converted to cyclopropylamine by the Hofmann reaction using aqueous alkali hypochlorite and alkali hydroxide for the hydrolysis. The chemistry of the Hofmann reaction has been summarized in "Organic Reactions", Vol. 3, 267-306 (1946).
This general reaction scheme can be represented by the diagram as follows: ##STR1##
The above reaction scheme, while starting with an inexpensive acetylene chemical, .gamma.-butyrolactone, involves the use of sodium metal in the manufacture of the fresh sodium methoxide needed for the ring closure. In plant scale manufacture, this presents considerable problems of safety in handling and the economics and overall yields on such a scale are also less than desirable.
There are several additional references in the literature to various chemical routes for the preparation of cyclopropylamine on a laboratory scale. Among these are: M. J. Schlatter, Journal of the American Chemical Society, 63, 1733 (1941); G. D. Jones, Journal of Organic Chemistry, 9, 484 (1944); W. D. Emmons, Journal of the American Chemical Society, 79, 6522 (1957). While convenient for laboratory use, the procedures in these cited articles are not suitable for large-scale commercial use due to low yields and/or use of expensive reagents.